Beyond the Basics: Endocrine Emergencies

CEU Review Form Endocrine Emergencies Part 2 (PDF)Valid until January 2, 2008

This is the second part of a two-part series addressing endocrine emergencies involving the thyroid gland. Refer to Part One in the October issue and online at www.emsresponder.com to review the anatomy and physiology necessary to completely understand normal thyroid function and hypothyroidism.

As you may recall from last month's article, hyperthyroidism produces a hypermetabolic state from an excessive amount of circulating thyroid hormone, resulting in emergencies such as thyroid storm and thyrotoxic crisis. Key findings include agitation, weight loss, nervousness and palpitations. Hypothyroidism, on the other hand, occurs when the thyroid gland secretes an inadequate amount or no thyroid hormone. The effects are generally opposite those of hyperthyroidism. The lack of circulating thyroid hormone reduces the basal metabolic rate, often producing subtle clinical signs and symptoms that may progress over several years. If the hypothyroidism condition becomes extreme, it may result in a severe depression in the metabolic rate and produce a potentially life-threatening emergency called myxedema coma.

EPIDEMIOLOGY
     Hypothyroidism may produce a variety of signs and symptoms. Some patients may remain subclinical, showing no obvious signs of the disease process and not realizing they have the condition until their thyroid hormone and thyroid-stimulating hormone levels are tested. Still other patients may present with hypothermia, a decreased mental state and other overt clinical signs of the life-threatening condition of myxedema coma. It is most often the latter patient who accesses the EMS system seeking emergency care for a condition that is not well recognized by patients.

     In the United States, the incidence of hypothyroidism is 4.6-5.8%, with 3.6-4.3% remaining subclinical in both men and women. Those with overt signs and symptoms of hypothyroidism comprise approximately 0.3-2.2%, with a small number representing males. The incidence in females has been reported to be anywhere from 2 to 10 times higher than in males, which may reflect an increased prevalence of autoimmune thyroid disease found in females. Even though hypothyroidism can occur at any time, the incidence increases with age. Onset of the disease often occurs between 40 and 50 years of age, with a peak incidence in patients in their 70s. The disease is found most often in the Caucasian population followed by Latinos. Hypothyroidism may be found in the African-American population, but at a rate that is approximately three times less than that of Caucasians. Because hypothyroidism produces a decrease in metabolic rate and does not allow the proper use of calories for energy and heat production by the body, patients often cannot tolerate low ambient temperatures. Thus, the incidence of hypothyroidism and myxedema coma increases in the winter months.

PATHOPHYSIOLOGY
     Hypothyroidism is associated with failure of the thyroid gland, which may result from a lack of or decrease in stimulation of the thyroid gland by other hormones. The release of thyroid hormone occurs as a result of the secretion and circulation of a cascade of hormones from other endocrine glands. Failure of any one of these hormones may produce hypothyroidism. Thyrotropin-releasing hormone (TRH) is secreted from the hypothalamus and is responsible for triggering the release of thyroid-stimulating hormone (TSH) from the anterior pituitary gland. Thyroid-stimulating hormone stimulates the release of thyroid hormone (TH) from the thyroid gland. Thus, a failure in the release of either TRH from the hypothalamus or TSH from the anterior pituitary gland will result in an inadequate secretion of thyroid hormone.

     Direct failure of the thyroid gland to secrete thyroid hormone is referred to as primary hypothyroidism. It is associated with the loss of thyroid gland tissue, predominantly due to autoimmunity. It can also result from failure following surgery or radioactive iodine ablation and accounts for up to 95% of causes of hypothyroidism. Low levels of circulating thyroid hormone cause a hypersecretion of thyroid-stimulating hormone from the anterior pituitary gland, leading to enlargement of the thyroid gland tissue and producing a goiter.

     Hypothyroidism resulting from failure of the anterior pituitary gland to secrete thyroid-stimulating hormone is referred to as secondary hypothyroidism; tertiary hypothyroidism is associated with failure of the hypothalamus to secrete thyrotropin-releasing factor. Both result in a low or absent level of circulating thyroid hormone, even though the thyroid gland itself is still functioning appropriately.

     Metabolically active cells require thyroid hormone. Without an adequate amount of circulating thyroid hormone, system-wide effects may be seen in a patient. These may include:

• Fatigue and excessive sleeping patterns of up to 12-14 hours per day
• Muscle sluggishness
• Bradycardia
• Decreased cardiac output
• Decreased myocardial contractility
• Decreased blood volume
• Gastric stasis of the gastrointestinal tract resulting in constipation
• Increased body weight
• Decreased hair growth
• Scaly skin
• Increased cholesterol and low-density lipoprotein (LDL) levels
• Increased insulin resistance
• Edematous appearance (myxedema).

     Myxedema is found in patients who have virtually no secretion of thyroid hormone. An increase in the amount of hyaluronic acid and chondroitin sulfate occurs. Both bind with protein and cause an excessive tissue gel to form in the interstitial spaces, resulting in an increase in the total interstitial fluid quantity and producing systemic edema. The interstitial tissue gel is not mobile; thus, the edema does not present as pitting. It is often exhibited as a puffy appearance, especially to the face and eyelids, and as bags under the eyes.

     Blood cholesterol and LDL levels increase due to an alteration of fat and cholesterol metabolism and decreased excretion of cholesterol in bile as a direct result of a decrease in circulating thyroid hormone. This produces an increase in atherosclerosis and arteriosclerosis, with a resultant increase in peripheral vascular disease and coronary artery narrowing.

     Myxedema coma is a syndrome representing an extreme decompensated state of hypothyroidism where the body is unable to maintain homeostasis. It is a rare condition that is difficult to recognize because it is poorly defined. Interestingly, the patient may not actually present in a true comatose state, even though the condition is termed myxedema coma. Usually, the patient presents with behavioral changes ranging from confusion to psychosis prior to the onset of coma. Often, the patient presents with a significantly decreased mental status, hypothermia, bradycardia, hypotension and respiratory acidosis.

     Precipitating factors of myxedema coma include:

• Cold exposure
• Infection (predominantly pulmonary)
• Congestive endocrine emergencies
• Trauma
• Hypoglycemia
• Hypoxia
• Hyponatremia (low blood sodium levels)
• Hemorrhage (predominantly gastrointestinal)
• Stroke
• Drugs (narcotics, anesthetics, benzodiazepines, phenothiazines, phenobarbital)
• Hypercapnia (elevated carbon dioxide levels).

     Myxedema coma is a true endocrine emergency. Life threats associated with severe hypothyroidism and myxedema coma include respiratory failure, hypotension and severely altered mental states. Hypothermia is also a very common finding. If a patient with myxedema presents with a normal temperature, one must suspect the possibility of an underlying infection. Respiratory failure is associated with depression of both the hypercapnic (high carbon dioxide) and hypoxic respiratory drives. High carbon dioxide levels in the blood typically produce confusion. Respiratory distress may occur as a result of upper airway obstruction associated with edema to the glottic opening and vocal cords. Myxedema capillaries are more permeable, which may result in slow-evolving pleural or pericardial effusion. The leaky capillaries may also result in ascites, which present with a distended abdomen.

ASSESSMENT
     Endocrine conditions often produce a wide variety of signs and symptoms. Hypothyroidism is no different. A patient with a mild case of hypothyroidism may develop myxedema coma following a physiologic stressor (e.g., trauma, stroke, hypoglycemia). This would produce a dramatic shift in clinical presentation from fairly mild signs and symptoms to severe manifestation of the life-threatening condition. It is difficult to separate the signs and symptoms of the two conditions, since myxedema coma is virtually an extreme case of hypothyroidism. Signs and symptoms of both hypothyroidism and myxedema coma are listed below:

• Cold intolerance (experienced by approximately 50% of patients)
• Weight gain (usually less than 15 pounds) with no increase in appetite
• Decreased energy
• Generalized weakness
• Muscle and joint pain or weakness
• Inability to concentrate
• Memory disturbances
• Constipation
• Hypothermia (found in 80% of patients with myxedema with temperatures as low as 75.2ºF in myxedema coma) with absence of shivering
• Blood pressure may be elevated, normal or low (myxedema coma typically presents with hypotension with systolic blood pressures less than 100 mmHg)
• Diastolic hypertension may be present
• Sinus bradycardia
• Generalized nonpitting edema (especially to the periorbital tissue)
• Skin is smooth, doughy, dry, waxy and cool
• Hair is dry and coarse
• Loss or thinning of eyebrows
• Loss of axillary and pubic hair
• Pallor
• Deep husky voice
• Goiter
• Paresthesias
• Unsteady gait and ataxia (lack of coordination)
• Dull facial expression
• Blurred vision
• Depression
• Headache
• Menstrual irregularity and painful menstruation
• Fullness in the throat.

     The signs and symptoms of severe hypothyroidism and myxedema coma, especially altered mental status and hypothermia, may be seen in other conditions. Sepsis- and cold-induced hypothermia may produce signs and symptoms similar to severe hypothyroidism or myxedema coma. It is important to take into account the entire patient history and physical assessment findings when considering a differential field diagnosis. Do not develop tunnel vision and fail to consider hypothyroidism in your differential field diagnosis, especially when faced with a patient presenting with decreased mental status, hypothermia, hemodynamic instability, bradycardia and respiratory failure.

MANAGEMENT
     Hypothyroidism may produce a wide range of signs and symptoms. Myxedema coma is a life-threatening condition that requires immediate emergency care that is primarily supportive, and expeditious transport. Consider the following emergency care when managing a patient with severe hypothyroidism or myxedema coma:

• Establish and maintain a patent airway. If the patient presents with an altered mental status or is comatose, it may be necessary to establish an airway by a manual maneuver and potentially a mechanical device, including endotracheal intubation in a severely altered mental state or coma. Sedatives, narcotics and anesthetics should not be administered; thus, facilitated endotracheal intubation should be avoided if possible.
• Establish and maintain an adequate ventilation status. If the patient's respiratory rate or tidal volume is inadequate, it is necessary to provide positive pressure ventilation. This may be necessary due to respiratory failure associated with a decreased respiratory drive in myxedema coma.
• Establish and maintain adequate oxygenation. Assess the patient for evidence of hypoxia. Apply a pulse oximeter and determine the SpO₂ reading. If there is either clinical evidence of hypoxia or an SpO₂ reading of less than 95% on room air, administer a high concentration of oxygen via a nonrebreather mask. If the patient is exhibiting no signs of hypoxia or the SpO₂ reading is greater than 95%, supplemental oxygen may be applied via a nasal cannula at 2 to 4 lpm, especially if any evidence of an altered mental status or congestive endocrine emergencies is exhibited during the history or physical exam.
• Provide continuous ECG monitoring. Patients experiencing severe hypothyroidism or myxedema coma may present with sinus bradycardia. Traditional management of sinus bradycardia may not be effective until the decreased thyroid hormone levels have been effectively managed.
• Initiate an intravenous line of normal saline. Hypotension may respond to an infusion of a crystalloid solution. A conservative fluid bolus should be the first line of management in hypotension. Due to the potential for cardiovascular insufficiency in these patients, be cautious with the infusion of fluids. Closely monitor oxygenation status and breath sounds for evidence of developing pulmonary edema. In severe cases or those in which the patient does not respond appropriately to fluids, consider vasopressor therapy. However, vasopressor therapy is typically not effective until thyroid hormone therapy has been initiated.
• Assess and determine the blood glucose level in the patient who presents with an acute behavioral change, altered mental status or coma. Consider hypoglycemia in your differential field diagnosis. If the blood glucose level is less than 60 mg/dL, administer 25 grams of 50% dextrose in water intravenously.
• Initiate passive rewarming if hypothermia is present. Remove any wet or cold clothing, cover the patient with blankets and turn up the heat in the ambulance patient compartment. Do not perform active rewarming, which may produce peripheral vasodilation and cause or exacerbate hypotension.
• If the patient is experiencing myxedema coma or a severe hypothyroid condition, consider rapid transport to an appropriate medical facility so definitive therapy to increase the thyroid hormone levels can be initiated. Untreated myxedema coma can be lethal.

CONCLUSION
     Even though the incidence and prevalence of hypothyroidism and myxedema coma is relatively low, EMS personnel must be prepared to understand the conditions and effectively manage the patient. It is important to consider hypothyroidism and myxedema coma in your differential field diagnosis when a patient presents with a severely altered mental status, hemodynamic instability, hypothermia, bradycardia and respiratory failure.

CEU Review Form Endocrine Emergencies Part 2 (PDF)Valid until January 2, 2008

Bibliography
Bledsoe BE, Porter RS, Cherry RA. Paramedic Care: Principles and Practice, Medical Emergencies, 2nd ed.
Upper Saddle River, NJ: Prentice Hall Health, 2006.
Guyton AC, Hall JE. Textbook of Medical Physiology, 10th ed. Philadelphia: W.B. Saunders, 2001.
Kwaku MP, Burman KD. Myxedema coma. J Intens Care Med 22: 224, 2007.
Marieb EN. Anatomy and Physiology, 2nd ed. San Francisco: Pearson Education, 2005.
Martini FH. Anatomy and Physiology. San Francisco: Pearson Education, 2005.
Marx JA, Hockberger RS, Walls RM. Rosen's Emergency Medicine: Concepts and Clinical Practice, 5th ed. St. Louis: Mosby, Inc., 2002.
Orlander PR. Hypothyroidism. www.emedicine.com/med/topic1145.htm.
Schraga ED. Hypothyroidism and Myxedema Coma. www.emedicine.com/emerg/topic280.htm.

Joseph J. Mistovich, Med, NREMT-P, is a professor and chair of the Department of Health Professions at Youngstown (OH) State University, author of several EMS textbooks and a nationally recognized lecturer.

William S. Krost, BSAS, NREMT-P, is an operations manager and flight paramedic with the St. Vincent/Medical University of Ohio/St. Rita's Critical Care Transport Network (Life Flight) in Toledo, OH, and a nationally recognized lecturer.

Daniel D. Limmer, AS, EMT-P, is a paramedic with Kennebunk Fire-Rescue in Kennebunk, ME. He is the author of several EMS textbooks and a nationally recognized lecturer.